Fractional flow reserve-guided percutaneous coronary intervention: When to use it?

ESC Congress News 2018 - Munich, Germany

29 Aug 2018

Late-breaking abstract presentations of further analyses of two prematurely halted trials provided valuable information about the utility of fractional flow reserve (FFR) measurement to guide treatment decisions in different patient populations with multivessel disease.

Topic(s):

Interventional Cardiology and Cardiovascular Surgery

On Saturday, Professor Gilles Rioufol (Hospices Civils de Lyon, Lyon, France) spoke about the prematurely halted Functional Testing Underlying Coronary Revascularization (FUTURE) trial. FUTURE was conducted at 31 centres in France with a planned enrolment of over 1,700 patients with multivessel disease. Stable all-comer coronary artery disease (CAD) patients referred for coronary angiography with at least two-vessel disease including the left anterior descending coronary artery, left main coronary artery or three-vessel disease, were randomised to management according to FFR guidance or to control angiographic guidance. In the FFR group, each ≥50% stenosis by visual estimation was tested for FFR. Any stenosis with FFR ≤0.80 was considered for revascularisation either by percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), while stenoses with FFR >0.80 were excluded from the revascularisation plan.

Prof. Rioufol explains, “After enrolment of just over 900 patients, the data safety monitoring and steering committee advised stopping the trial in view of a more than two-fold increase in overall mortality in the FFR group. Of note, the one-year outcome data available for nearly 800 patients did not show a significant difference in the composite primary endpoint of all-cause mortality, myocardial infarction (MI), stroke or unplanned coronary revascularisation.” When Prof. Rioufol presented these findings at American Heart Association Scientific Sessions 2016,(1) there was much speculation as to why mortality was increased—at ESC Congress 2018, he provided final results and further insight.

The safety analysis confirmed a higher mortality in the FFR group compared with the control group at one year (hazard ratio 2.39; p=0.038). “However,” says Prof. Rioufol, “in the intention-to-treat analysis, there was no difference in the incidence of the primary endpoint between the FFR and the control group at one year (14.4% vs 14.6%; p=0.94). The mean Syntax score was higher in the FFR group compared to the control group when revascularisation with PCI was chosen (19±7 vs 17±7; p=0.007). Notably, patients with a Syntax score ≥32 had a higher risk of adverse outcomes in the FFR group compared to the control group (p=0.02).”

He explains, “Using FFR to select a revascularisation strategy in this subset of complex patients appears to increase mortality in patients with a Syntax score ≥32 by lowering their functional ischaemic severity. Our results suggest caution when using FFR in patients with complex multivessel disease not obviously amenable to PCI.”

“This analysis of FUTURE is reassuring for FFR. It’s not a device-related problem but is more linked to strategy.”

Commenting on the results, Prof. Rioufol observes, “FUTURE was a trial questioning if FFR could help to improve revascularisation strategy in patients with multivessel disease. It absolutely did not challenge the role of FFR for PCI-eligible patients.” He continues, “We observed that FFR decreased the rate of revascularisation with a two-fold increase of medical treatment only, and these patients fared very well. This is a good news. We also observed that PCI was the dominant choice of revascularisation (only 12% for CABG) and that was quite a surprise because inclusion criteria left room for the options of PCI or CABG. In that specific context, with the choice of treatment decided centre by centre according to local practices, we observed that PCI remained the dominant strategy, even when anatomy was very complex according to the Syntax score and these patients had a worse outcome.”

Yesterday, Doctor Stephane Fournier (Cardiovascular Center Aalst, Aalst, Belgium) presented results from a sub-analysis of the Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME 2) trial. FFR was measured in all stenoses in patients with stable CAD for whom PCI was being considered.(2) Patients with at least one stenosis measuring FFR ≤0.80 were randomised to FFR-guided PCI or medical therapy alone. The primary endpoint was a composite of death, MI or urgent revascularisation. Recruitment was halted prematurely after randomisation of 888 patients because of a significant between-group difference. Dr. Fournier explains, “The original analysis showed that in patients with stable CAD and functionally significant stenoses, FFR-guided PCI decreased the need for urgent revascularisation compared with medical therapy alone. Here we investigated outcomes in 98 participants with silent ischaemia—which is thought to have particularly poor outcomes—compared with the remaining symptomatic patients.”

“Among patients receiving medical therapy alone, the rate of death or MI was significantly higher in silent compared with symptomatic ischaemia (31.1% vs 14.4%, respectively; p=0.002),” he says, continuing, “However, in patients receiving PCI, there was no significant difference in this endpoint between silent and symptomatic ischaemia (9.4% vs 12.2%; p=0.497).” Dr. Fournier notes that, “Death or MI were significantly lower in patients with silent ischaemia who were randomised to PCI compared with medical therapy alone (9.4% vs 31.1%; p=0.003).”

“The excess in adverse outcomes in patients with silent ischaemia appears to be abolished by FFR-guided PCI.”

“Symptomatic patients randomised to medical therapy alone more often cross over to PCI, which presumably protects them from death or MI,” he adds.

ESC Congress is the world’s largest and most influential cardiovascular event contributing to global awareness of the latest clinical trials and breakthrough discoveries. ESC Congress 2018 takes place 25 to 29 August at the Messe München in Munich, Germany. Explore the scientific programme.